A biofluid signature comprising sTWEAK in semen, serum fasting glycemia and the mRNA levels of Fn14, KLK2, CXCR2 and CCR3 in semen cell sediment, combined with total serum PSA levels, represents a non-invasive biomarker panel with high negative predictive value that can be used to classify PCa aggressiveness. Here, KLK3 is linked to posterior cortical atrophy.